Effects of midazolam and flunitrazepam on the release of dopamine from rat striatum measured by in vivo microdialysis

Abstract

We have studied the effects of midazolam and flunitrazepam on extracellular concentrations of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in rat striatum in freely moving animals using in vivo microdialysis. I.v. injections of midazolam 0.075 and 0.15 mg kg-1 decreased striatal dopamine concentrations in a dose-dependent manner without affecting the concentrations of DOPAC and HVA. Flunitrazepam 0.015 and 0.03 mg kg-1 also decreased striatal dopamine concentrations in a dose-related manner, but the reductions in DOPAC and HVA were not significant. Flumazenil 6 micrograms kg-1 alone did not affect striatal concentrations of dopamine, DOPAC and HVA, but it prevented the effects of midazolam and flunitrazepam. Flunitrazepam 10 mumol litre-1 also decreased striatal dopamine release when infused through a dialysis probe placed into the striatum, but it failed to affect striatal dopamine release when infused into the ipsilateral substantia nigra. Central administrations of midazolam were effective only when the drug was infused into both sites simultaneously (10 and 100 mumol litre-1) or given by intraventricular injection (0.5 and 1 micrograms). These results suggest that midazolam and flunitrazepam affect striatal dopamine release in a different manner.